The effect of colchicine on cholesterol crystal formation, expansion and morphology: a potential mechanism in atherosclerosis

Autor: Zain Ul Abideen, Dorothy R. Pathak, Rand Sabanci, Megan Manu, George S. Abela
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Frontiers in Cardiovascular Medicine, Vol 11 (2024)
Druh dokumentu: article
ISSN: 2297-055X
DOI: 10.3389/fcvm.2024.1345521
Popis: BackgroundInflammation is pivotal to the progression of atherosclerosis. Cholesterol crystals (CCs) that grow and enlarge within the plaque core can cause plaque rupture and trigger inflammation as they deposit into the atherosclerotic bed. Thus, agents that affect CC formation, expansion, and morphology may reduce cardiovascular (CV) risk independent of lipid-lowering and anti-inflammatory therapy.ObjectiveBecause colchicine is highly concentrated in leukocytes that can enter the atherosclerotic plaque core, we tested its effect on the formation and growth of CCs in bench experiments to determine whether it may have direct effects on CCs, independent of its known anti-inflammatory actions.MethodDifferent dosages of colchicine mixed with cholesterol (0.05–5 mg/ml/g of cholesterol) were used to influence the formation CCs and volume expansion in vitro. These were compared to control samples with cholesterol in ddH2O without colchicine. In an ex vivo study, fresh atherosclerotic human plaques were incubated with and without colchicine in a water bath at 37°C for 48 h to assess the impact of colchicine on CC morphology. Scanning electron microscopy (SEM) was utilized to analyze CC morphology in samples from the various treatment groups.ResultsThe addition of colchicine to cholesterol caused a substantial dose-dependent reduction in volume (p
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